The aim of this project is to gain greater understanding into the psychobiology of the illness of schizophrenia. Three principal areas of research have been begun during the past year: the phenomenology and biochemistry of neuroleptic response, neuropsychiatric aspects of schizophrenia, and clinical and biological correlates of depressive and "negative" symptoms in schizophrenia. Clinical research for this project is carried out on the 4-East Nursing Service of the Clinical Center. Patients with DSM III diagnosed schizophrenia are studied during a several month research period during which they are administered neuroleptic and placebo medications under double-blind conditions. Plasma determinations for levels of HVA, MHPG and 5-HIAA are performed throughout this period of study. Clinical changes associated with neuroleptic administration and discontinuation are examined with relationship to levels of amine metabolites. This portion of the project is aimed towards gaining a better understanding of the mechanism of neuroleptic action in schizophrenia. Recent high-technology strategies have become available in clinical neuroscience research. Computer axis tomography, positron emission tomography and sophisticated evoked potential systems are now available for use in the study old schizophrenia. We have attempted to utilize these strategies to study possible neuroanatomic and neurophysiologic abnormalities which may relate to the etiology or pathophysiology of schizophrenia. A third portion of this research program studies depressive and "negative" symptomatology during the course of the schizophrenia illness. This work includes the application to patients with schizophrenia of biological tests currently employed in studying depressive illness and phenomenologic study of interrelationships between depressive and "negative" symptoms. Systematic investigation into suicidal behavior in schizophrenic patients is also currently in progress.